Clinical transplantation therapy of human organs such as the lung, heart, liver, kidney and pancreas has been already practiced and conducted routinely. However, a problem of lack of donors for patients waiting for transplantation who have increased year by year has become serious, and a time to wait till operation has been extended. Even though donors of organ transplantation appear, long-term preservation or supply system of blood or the like has not been currently established well.
Especially in the organ transplantation, the low temperature preservation is mainly conducted, and a time limit of preservation is approximately 4 to 24 hours. Accordingly, urgent establishment of preservation and revival techniques has been in demand. Actually, in the low temperature preservation and revival of the heart extracted from a rat, a rabbit or a baboon using University of Wisconsin Solution (UW solution), the time limit is 6 to 18 hours. In the successful transplantation of the rat's heart by preservation with a combination of this UW solution and a perfluorocarbon medium, the time limit is 24 hours (all of five rats) to 48 hours (four of five rats). The reason is that when the extracted heart is exposed to a low temperature of 4° C. or ischemic disorder, a cell membrane is damaged and thus tissue cells cannot be revived.
When an organ of a patient is seriously damaged and recovery is not expected by ordinary treatment, organ transplantation is conducted which is therapy by transplanting an organ of a donor in a recipient. A donor includes a living person and a dead person, and a dead donor includes a dead person by heart death and a dead person by cerebral death. Under the existing law (“Law regarding Organ Transplantation” effective on Oct. 16, 1997), a declaration of intention of a donor himself is required for organ extraction in both cases. In Japan with life and death thought based on Buddhism thought, donors who make a declaration of intention as an organ donor before death are quite few, and the number of donors is overwhelmingly small in comparison with the number of recipients.
When an organ is extracted from a living body or a donor is dead, its viability is rapidly lost. When an organ poor in viability is transplanted, it is destroyed within a body of a recipient without exhibiting the predetermined function despite good histocompatibility of the organ. Accordingly, apart from the problem of the histocompatibility, it is no exaggeration to say that whether or not organ transplantation is successful depends on how a time that lapses from extraction of an organ to transplantation thereof can be shortened. Since donors are now very few, there is a rare case that a donor resides near a recipient. Therefore, in a site of organ transplantation, an information on donors has been often exchanged usually, or a time that lapses from extraction of an organ to transplantation thereof has been shortened as much as possible by transporting an extracted organ via a helicopter or a jet. However, it is quite clear that such a method depending on a transportation time is limited. For overcoming this limitation, diverse preservative agents for low temperature preservation of organs have been contrived.
As an organ preservative agent which has been put to practical use, an EuroCollins solution comprising glucose and various electrolytes and a UW solution comprising an impermeable component, an oncotic pressure component, an energy metabolism acceleration component and hormone have been well known. It has been said that the EuroCollins solution is effective for the kidney having high viability, while an effect of protection for tissues and cells other than the kidney is not satisfactory. Further, it has been said that the UW solution has defects that it is unstable as a pharmaceutical preparation and has to be preserved at a low temperature after formulation.
As an organ preservative agent free from such detects, Patent Document 1 proposes an organ preservative agent comprising trehalose, hydroxyethyl starch and various electrolytes, and Patent Documents 2 to 4 propose an organ preservative agent comprising potassium L-ascorbic acid DL-α-tocopherol phosphoric acid diester (hereinafter abbreviated as “EPC-K”) as a synthetic substance. However, the former organ preservative agent involves problems that since the molecular weight and the degree of substitution of the hydroxyethyl starch as a synthetic substance have to be adjusted to quite limited ranges, it is difficult to formulate the pharmaceutical preparation and maintain homeostasis. Since EPC-K used in the latter organ preservative agent is low in solubility in water and has various pharmacological activities, the mixing amount of EPC-K has to be decreased or the use of the agent itself has to be abandoned sometimes for reasons of recipients.
Patent Document 1: gazette of JP-A-6-40801
Patent Document 2: gazette of JP-A-6-166624
Patent Document 3: gazette of JP-A-7-215801
Patent Document 4: gazette of JP-A-7-330501